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Tissue Engineering. Part C, Methods Jun 2024The synthesis and assembly of mature, organized elastic fibers remains a limitation to the clinical use of many engineered tissue replacements. There is a critical need...
The synthesis and assembly of mature, organized elastic fibers remains a limitation to the clinical use of many engineered tissue replacements. There is a critical need for a more in-depth understanding of elastogenesis regulation for the advancement of methods to induce and guide production of elastic matrix structures in engineered tissues that meet the structural and functional requirements of native tissue. The dramatic increase in elastic fibers through normal pregnancy has led us to explore the potential role of mechanical stretch in combination with pregnancy levels of the steroid hormones 17β-estradiol and progesterone on elastic fiber production by human uterine myometrial smooth muscle cells in a 3D culture model. Opposed to a single strain regimen, we sought to better understand how the amplitude and frequency parameters of cyclic strain influence elastic fiber production in these myometrial tissue constructs (MTC). Mechanical stretch was applied to MTC at a range of strain amplitudes (5%, 10%, and 15% at 0.5 Hz frequency) and frequencies (0.1 Hz, 0.5 Hz, 1 Hz, and constant 0 Hz at 10% amplitude), with and without pregnancy-level hormones, for 6 days. MTC were assessed for cell proliferation, matrix elastin protein content, and expression of the main elastic fiber genes, elastin (ELN) and fibrillin-1 (FBN1). Significant increases in elastin protein, and ELN and FBN1 mRNA were produced from samples subjected to a 0.5 Hz, 10% strain regimen, as well as samples stretched at higher amplitude (15%, 0.5 Hz) and higher frequency (1 Hz, 10%); however, no significant effects due to third-trimester mimetic hormone treatment were determined. These results establish a minimum level of strain is required to stimulate the synthesis of elastic fiber components in our culture model, and show this response can be similarly enhanced by increasing either the amplitude or frequency parameter of applied strain. Further, our results demonstrate strain alone is sufficient to stimulate elastic fiber production and suggest hormones may not be a significant factor in regulating elastin synthesis. This 3D culture model will provide a useful tool to further investigate mechanisms underlying pregnancy-induced de novo elastic fiber synthesis and assembly by uterine smooth muscle cells.
PubMed: 38943281
DOI: 10.1089/ten.TEC.2024.0038 -
Maternal & Child Nutrition Jun 2024Approximately half of pregnant women in India are anemic, representing over 7.5 million women. Few studies have assessed the relationship between multiple micronutrient...
Approximately half of pregnant women in India are anemic, representing over 7.5 million women. Few studies have assessed the relationship between multiple micronutrient deficiencies and anemia during pregnancy or the trajectory of hemoglobin (Hb) during pregnancy in low-resource settings. We enrolled 200 pregnant women from the Maternal and Newborn Health (MNH) registry, a population-based pregnancy and birth registry in Eastern Maharashtra, India to address these gaps. The women provided capillary (finger-prick) and venous blood specimens at enrollment (<15 weeks), and a second capillary specimen in the 3rd trimester (>27 weeks). Capillary specimens were analyzed at the time of collection with a HemoCue Hb 201+; venous specimens were shipped on dry ice to a laboratory for cyanmethemoglobin assessment. In the 1st trimester, mean Hb concentration and anemia (Hb<11.0 g/dL) prevalence using capillary specimens were 10.9 ± 1.5 g/dL and 51.1%; mean Hb concentration using venous blood specimens was estimated to be 11.3 ± 1.3 g/dL and anemia prevalence was 37.5%. The prevalence of iron, vitamin B and folate deficiencies were 40%, 30% and 0%, respectively. Among women with anemia in the 1st trimester (venous blood), 56% had concurrent iron deficiency (inflammation-adjusted serum ferritin <15 µg/L) indicating that their anemia may be amenable to iron supplementation. In total, 21% of women had ID and anemia, 19% ID in the absence of anemia, 16.5% anemia in the absence of ID and 43.5% had neither. By the 3rd trimester, mean Hb from capillary specimens had declined to 10.1 ± 1.35 g/dL and anemia prevalence increased to 70.7%, despite 99.4% mothers reporting receipt of iron-folic acid (IFA) supplements during her current pregnancy, and 83.9% reporting IFA consumption the previous day. Significant predictors of anemia in the 1st trimester (both venous and capillary) included the number of weeks gestation at the time of Hb assessment and inflammation-adjusted serum ferritin. For 3rd trimester anemia, significant predictors included 1st trimester height, BMI and IFA consumption during the 3rd trimester (but not 1st trimester micronutrient biomarkers), indicating that IFA supplementation over the course of pregnancy may have influenced micronutrient status and anemia risk. Our findings highlight the severity of the burden of anemia and micronutrient deficiencies in Eastern Maharashtra, but also highlight that in many cases, ID and anemia affect different individuals. Preventing and managing anemia in pregnancy in India will require strengthening both clinical and community-based strategies targeting iron deficiency, as well as other causes of anemia.
PubMed: 38943254
DOI: 10.1111/mcn.13684 -
BMC Pregnancy and Childbirth Jun 2024Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the...
BACKGROUND
Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the pre-pregnancy dietary phytochemical index (DPI) on gestational diabetes mellitus (GDM).
METHODS
In this prospective cohort study 1,856 pregnant women aged 18-45 years who were in their first trimester, were recruited and followed up until delivery. The dietary intakes of participants were examined using an interviewer-administered validated 168-item semi-quantitative food frequency questionnaire (FFQ). Inverse probability weighting (IPW) of propensity scores (PS), estimated from the generalized boosted model (GBM) were used to obtain a adjusted risk ratio (aRR) for potential confounders.
RESULTS
During the follow-up period, 369 (19.88%) women were diagnosed with GDM. DPI scores ranged from 6.09 to 89.45. There was no association between DPI scores and GDM (aRR: 1.01, 95% confidence interval [CI]: 0.92, 1.08; p trend = 0.922). When comparing DPI quartile 4 (most pro-phytochemical content) to quartile 1 (few phytochemical contents), there was no significant difference between them (aRR: 0.97; 95% CI: 0.75, 1.25; p = 0.852). Also, there was no significant difference between DPI quartile 3 and quartile 1 (aRR: 1.04; 95% CI: 0.81, 1.34; p = 0.741) as well as DPI quartile 2 and quartile 1 (aRR: 0.92; 95% CI: 0.71, 1.21; p = 0.593).
CONCLUSIONS
Although this data did not support the association between pre-pregnancy DPI scores and GDM, further cohort studies to ascertain the causal association between them are warranted.
Topics: Humans; Female; Pregnancy; Diabetes, Gestational; Adult; Prospective Studies; Young Adult; Phytochemicals; Diet; Adolescent; Middle Aged; Risk Factors; China; Pregnancy Trimester, First; Cohort Studies
PubMed: 38943050
DOI: 10.1186/s12884-024-06643-4 -
Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
Environmental Pollution (Barking, Essex... Jun 2024Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air...
Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM), and nitrogen dioxide (NO). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM, NO, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM concentration (3.20 μg/m) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2 (-7.99%, 95% CI: -13.8%, -2.23%) or 3 trimester (-2.81%, 95% CI: -10.0%, 4.38%). The average cumulative PM exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.
PubMed: 38942277
DOI: 10.1016/j.envpol.2024.124463 -
The American Journal of Clinical... Jun 2024The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some...
BACKGROUND
The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child.
OBJECTIVE
To determine the association between pregnancy weight gain below the lower limit of the current Institute of Medicine (IOM) recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity.
METHODS
We used data from a prospective cohort study of US nulliparae with prepregnancy overweight (n=955) or obesity (n=897) followed from the first trimester to 2-7 years postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity).
RESULTS
Pregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of -2 standard deviations in pregnancies with overweight (equivalent to 3.6kg at 40 weeks) and obesity (-2.8kg at 40 weeks) were 0.99 (0.91, 1.06) and 0.97 (0.87, 1.07).
CONCLUSIONS
These findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy BMI groups.
PubMed: 38942117
DOI: 10.1016/j.ajcnut.2024.06.011 -
Reproductive Biology Jun 2024Mesenchymal cells within theplacental villi play a crucial role in shaping the morphology of branching structures and driving the development of blood vessels. However,...
Mesenchymal cells within theplacental villi play a crucial role in shaping the morphology of branching structures and driving the development of blood vessels. However, the markers and functions of placental villous pericytes (PVPs) as distinct subgroups of placental villous mesenchymal cells, remain unclear. Therefore, in this study, the markers and functions of PVPs were investigated. Single-cell sequencing data from the first-trimester placental villi was obtained and the Seurat tool was used to identify PVP markers. Gene Ontology (GO) analysis of specific genes was performed using the DAVID database. The Cellchat tool was employed to investigate the interaction signals between the PVPs and other cells. Expression of the PVP markers was confirmed using immunofluorescence. Presence of extracellular vesicles in the placental villous mesenchyme and PVPs was examined by transmission electron microscopy. Our findings revealed that renin (REN) and amphiregulin (AREG)-positive fibroblasts in the placental villi specifically expressed several classic pericyte markers. In the first trimester, certain conserved functions of pericytes were observed and they displayed tissue-specific functions such as in the integrin-mediated signaling pathway and extracellular exosomes. Moreover, the placental villous mesenchyme was found to be rich in extracellular vesicles. AREG is specifically transcribed in the first trimester PVPs, however, its protein was located in syncytiotrophoblasts. These insights contribute to a comprehensive understanding of early placental development and offer new therapeutic targets for placenta-derived pregnancy complications.
PubMed: 38941941
DOI: 10.1016/j.repbio.2024.100919 -
JAMA Network Open Jun 2024Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations....
IMPORTANCE
Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations. Consequently, professional bodies advise against the use of varenicline and bupropion and recommend caution with nicotine replacement therapy (NRT). Contemporary estimates of the use of smoking cessation pharmacotherapies during pregnancy are lacking.
OBJECTIVE
To quantify the proportion of individuals using prescribed smoking cessation pharmacotherapies during pregnancy and during the first trimester specifically, in 4 countries.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study used linked birth records, hospital admission records, and dispensing records of prescribed medications from all pregnancies resulting in birth between 2015 and 2020 in New South Wales, Australia; New Zealand; Norway; and Sweden. Data analyses were conducted in October and November 2023.
EXPOSURE
Prescribed smoking cessation pharmacotherapy use (varenicline, NRT, and bupropion) during pregnancy was defined as days' supply overlapping the period from date of conception to childbirth.
MAIN OUTCOMES AND MEASURES
Prevalence of use among all pregnancies and pregnancies with maternal smoking were calculated. Among women who used a pharmacotherapy, the proportion of women with use during the first trimester of pregnancy was also calculated.
RESULTS
Among 1 700 638 pregnancies in 4 countries, 138 033 (8.1%) had maternal smoking and 729 498 (42.9%) were younger than 30 years. The prevalences ranged from 0.02% to 0.14% for varenicline, less than 0.01% to 1.86% for prescribed NRT, and less than 0.01% to 0.07% for bupropion. Among pregnant individuals who smoked, use of pharmacotherapies was up to 10 times higher, with maximum prevalences of 1.25% for varenicline in New South Wales, 11.39% for NRT in New Zealand, and 0.39% for bupropion in New Zealand. Use in the first trimester occurred among more than 90% of individuals using varenicline, approximately 60% among those using NRT, and 80% to 90% among those using bupropion.
CONCLUSIONS AND RELEVANCE
In this cohort study of pregnant individuals in 4 high-income countries, the low prevalence of varenicline and bupropion use during pregnancy and higher prevalence of NRT use aligned with current clinical guidelines. As most use occurred in the first trimester, there is a need for evidence on the risk of congenital malformations for these medications.
Topics: Humans; Female; Pregnancy; Smoking Cessation; Adult; Retrospective Studies; Smoking Cessation Agents; Varenicline; Bupropion; New Zealand; Tobacco Use Cessation Devices; Pregnancy Complications; Sweden; New South Wales; Norway; Young Adult; Smoking; Pregnancy Trimester, First
PubMed: 38941092
DOI: 10.1001/jamanetworkopen.2024.19245 -
International Journal of Gynaecology... Jun 2024With inconsistencies regarding the possible effect of hyperemesis gravidarum on the course of pregnancy, this research aimed to study the association between hyperemesis...
OBJECTIVE
With inconsistencies regarding the possible effect of hyperemesis gravidarum on the course of pregnancy, this research aimed to study the association between hyperemesis gravidarum and pregnancy outcomes, while also addressing the trimester of diagnosis and severity.
METHODS
A retrospective cohort study was performed, including all singleton deliveries of mothers from the largest health maintenance organization in the country, in a single tertiary hospital between 1991 and 2021. The incidence of adverse pregnancy outcomes was compared between pregnancies with and without hyperemesis gravidarum diagnosis. Multivariable generalized estimation equation binary models were used to study the association between maternal hyperemesis gravidarum, trimester of diagnosis and hyperemesis gravidarum severity and the studied outcomes.
RESULTS
The study population included 232 476 pregnancies, of which 3227 (1.4%) were complicated with hyperemesis gravidarum. Women with hyperemesis gravidarum were more likely to deliver preterm (adj. OR = 1.33, 95% CI: 1.18-1.50), a newborn with low birthweight (adj. OR = 1.52, 95% CI: 1.16-1.98, only if diagnosed in the second trimester), and to have a cesarean delivery (adj. OR = 1.20, 95% CI: 1.09-1.32). They were less likely to deliver small gestational age newborn (adj. OR = 0.82, 95% CI: 0.69-0.99) and their offspring to experience perinatal mortality (adj. OR = 0.54, 95% CI: 0.31-0.93, among mild cases only). A dose-response association was observed between preterm birth and hyperemesis gravidarum (adj. OR = 1.26; 95% CI: 1.11-1.44, for mild cases and adj. OR = 2.04; 95% CI: 1.31-3.19, for severe cases).
CONCLUSIONS
Hyperemesis gravidarum is associated with an increased risk for adverse pregnancy outcomes including mainly preterm delivery in a dose-response manner and when diagnosed during the second trimester.
PubMed: 38940074
DOI: 10.1002/ijgo.15760 -
Cureus May 2024The management of symptomatic hydronephrosis presents substantial challenges due to the absence of consensus within clinical guidelines concerning pain management,... (Review)
Review
The management of symptomatic hydronephrosis presents substantial challenges due to the absence of consensus within clinical guidelines concerning pain management, diagnostic approaches, therapeutic interventions, and follow-up protocols. This literature review focuses on complexities involving diagnostic challenges that arise from the difficulty in distinguishing physiological from pathological obstruction and treatment complexities that involve deciding on the most appropriate pain management medications and safe interventions while minimizing risks to both the mother and foetus. To address these challenges, a comprehensive search of electronic databases, including PubMed, Embase, and Google Scholar, was conducted for the terms "hydronephrosis", "hydronephrosis in pregnancy", "ionising radiation in pregnancy", and "safe analgesia in pregnancy". Moreover, Mendeley software was used to collect and organize the references. Diagnostic complexities involve selecting the appropriate imaging modality that balances accurate diagnosis with minimal radiation to the foetus. Ultrasound remains the first-line option. However, it has limitations in delineating the underlying aetiology. MRI avoids ionizing radiation but has restricted utility due to foetal movement artifacts. CT provides the highest diagnostic accuracy but raises foetal radiation exposure concerns, though ultra-low dose protocols (<1 mGy) are deemed acceptable by most guidelines. Management includes either a conservative approach, which is a safe option in the majority of cases, or intervention with a percutaneous nephrostomy or ureteric stent insertion, both with comparable symptom control. However, there is no consensus on the optimal frequency for drain changes to prevent rapid encrustation. Definitive procedures like ureteroscopy and percutaneous nephrolithotomies remain controversial. Most guidelines suggest limiting these interventions to specialist centres during the second trimester if required.
PubMed: 38939245
DOI: 10.7759/cureus.61240